This work is a competing continuation of NIH R01 AR46996, "New Optically Based Model for Assessing Cartilage Repair and Protection". A variety of modalities, ranging from cartilage transplant to Pharmaceuticals, have demonstrated considerable promise as methods for altering the progression of osteoarthritis (OA). This has resulted in heightened interest in methods for assessing early OA changes both in humans and animals and is the reason the NIH has put forward the OA initiative. Currently, animal models including rabbits, rats, and dogs involve sacrificing groups of animals at given time points and analyzing joint changes with histology. This approach to using animal models has several drawbacks. First, rather than following the time course of the disease in a given animal, data for each animal is obtained only at a single time point. Second, since individual data is obtained at only one time point, large numbers of animals are required for time course studies. Therefore, experiments tend to be expensive due to the costs of the large numbers of animal and the cost associated with tissue processing. Third, only limited quantities of the given therapeutic may be available. Finally, large animals are often only used because of the small amount of tissue available for analysis in small animal models. A technology capable of identifying changes in OA joints in small animals in real time, near the resolution of histology, and without the need for animal sacrifice could be a powerful tool for assessing the efficacy of therapeutic agents. The objective of this proposal is the continued development of an imaging based animal model(s) for the evaluation of therapeutics designed to treat OA cartilage. Specifically, the focus of this work is that optical coherence tomography (OCT), when combined with a rat model(s) of OA, will demonstrate unique advantages for the evaluation of potential therapeutics. It is postulated that the proposed model, in addition to increasing information on the efficacy of therapeutics, will reduce the number of animals that need to be sacrificed, the quantity of tissue requiring processing, and the amount of therapeutic needed. Furthermore, technological advances can be directly transferred to in vivo human applications. OCT is analogous to ultrasound B mode imaging using infrared light rather than acoustical waves(1,2). We have demonstrated with previous work that OCT can identify the internal microstructure of articular cartilage at a resolution up to 25X higher than any clinical imaging technology. This has included the micron scale delineation of fibrillations, cartilage width, and the presence of fibrocartilage. The hypothesis of this proposal is that the application of OCT to an OA rat model performed in the previous funding period can be substantially improved. The hypothesis will be tested through both advances in OCT technology and the use of rat models that more closely resembles OA development in humans. This will be achieved through both modifications of the OCT system and the animal model used. The specific aims to test the hypothesis are: Aim 1. Modifying the OCT system to Monitor OA at Earlier Stages and with Greater Sensitivity. Aim 2. Examining the Combination of OCT with Several Surgical Models of OA in the Rat. 3. Examining the Combination of OCT with the Microawl Therapeutic Technique in a Surgical Rat Model of OA. 4. Examining the Combination of OCT with a Pharmaceutical Intervention in Surgical Rat Model of OA.